Changing therapeutic landscape - The last decade

Undoubtedly the most important event in the previous decade in lymphoma treatment was the establishment of immunotherapy as a prime modality. Addition of rituximab improves survival in almost every group of patients with CD20+ tumors. This has led to the appearance of a number of "me too" monoclonal antibodies (MoAbs) as well as MoAbs directed against other antigens whose usefulness remains to be proven during the next decade. We have also seen the raise and, probably unwarranted, fall of radioimmunotherapy. Conventional radiotherapy is losing ground. Regarding chemotherapy, the success of attempts to supplant R-CHOP-21 for front-line treatment of DLBCL with more dose-dense or dose-intense regimens remains doubtful and this issue is still unresolved. Bendamustine appeared as possibly the most effective cytotoxic agent for treatment of indolent lymphomas, while treatment of HL is becoming more tailored to prognostic features. This decade has also seen the advent of targeted drugs for lymphoma treatment. Their real impact will become known in the years to come. Finally, we may hope that advances in understanding the biology of lymphomas, made in the last decade, will help resolve remaining critical issues, treatment of T-NHLs and high-risk DLBCLs, being probably the most prominent

Hodgkin Lymphoma: Comments on ESMO Clinical Practice Guidelines

No abstract availabl

FNA based diagnosis of head and neck nodal lymphoma [Citomorfološka dijagnoza limfoma u području glave i vrata]

Fine-needle aspiration (FNA) biopsy has become a well established technique in the diagnosis, staging, and follow-up of patients with head and neck lesions. As in lymphoma diagnostics, FNA serves as a screening method in evaluating potentially affected lymph node for open or core biopsy. According to the World Health Organization classification of lymphoid neoplasms, today it is important to recognize cell morphology and reveal its phenotype, then combine it with different genotypic information and clinical data to provide appropriate therapy. The aim of this study was to assess the efficacy of FNA and immunocytochemistry based lymphoma diagnostic in head and neck region. We conducted a retrospective study during a period of three years where cases with either FNA diagnosis or clinical suspicion of newly recognized or relapsing lymphoma were reviewed. In the study were included patients that were referred to our laboratory from hematology department, in whom head and neck lymphadenopathia was found and lymph node FNA preceded other procedures. Two hundred eighty-five aspirations from 248 patients fulfilled study criteria. Adequate specimens were diagnosed as lymphoma in 100 cases (36%), in 65 male and 35 female patients, 76 in patients with newly discovered disease and 24 in patients with prior lymphoma diagnosis. Overall sensitivity of FNA specimens in the diagnosis of head and neck lymphomas was 90%, specificity 88%, predictive value of a positive result 97%, and predictive value of negative result 61%. Based on our results FNA corroborated with immunophenotyping by immunocytochemistry can be method of choice in primary lymphoma diagnosis as a method complementary to histopathology in lymphoma diagnostics

Treatment of patients with advanced Hodgkin’s lymphoma with escalated BEACOPP

Cilj: Svrha rada je pokazati rezultate, kao i nuspojave, u bolesnika s Hodgkinovim limfomom stadija III ili IV, koji su liječeni s 4 ciklusa eBEACOPP-a i 4 ciklusa sBEACOPP-a. Metode: U razdoblju od listopada 2003. do ožujka 2011. godine liječeno je 15 bolesnika. Medijan dobi bio je 28 godina (19 – 47), s medijanom praćenja od 14 mjeseci (1 – 90). Svi su bolesnici liječeni s 4 ciklusa eBEACOPP-a, 11 bolesnika liječenje je nastavilo s 4 ciklusa sBEACOPP-a, kod 3 bolesnika, zbog značajnih nuspojava, primijenjen je program ABVD, dok je jedan bolesnik (plućna toksičnost) liječen programom COPP. Rezultati: U 10 bolesnika liječenjem je postignuta kompletna remisija bolesti, a u 5 bolesnika parcijalna remisija bolesti; ukupan odgovor na terapiju bio je 100 %. U 5 bolesnika koji su postigli parcijalnu remisiju bolesti provedena je radioterapija. Nakon praćenja od 14 mjeseci, preživljenje bez znakova bolesti, kao i ukupno preživljenje, iznosi 100 %. Kod većine bolesnika primijećena je ozbiljna hematotoksičnost, a 5 bolesnika (33 %) je zbog febrilne neutropenije liječeno bolnički. Rasprava i zaključak: Ova preliminarna studija potvrđuje da je program liječenja eBEACOPP-om izrazito učinkovit, a rezultati su u skladu s rezultatima dosad provedenih studija. Radi se o malom uzorku bolesnika s kratkim razdobljem praćenja. Treba naglasiti da za sada nisu zamijećeni rani relapsi bolesti. Toksičnost je značajna, naročito hematotoksičnost uz neutropenijske vrućice.Aim: We present the outcome and toxicity of intensive chemotherapy protocol escalated BEACOPP (eBEACOPP 4 cycles) followed by standard BEACOPP (sBEACOPP 4 cycles). Methods: From October 2003 untill March 2011, 15 patients were treated with eBEACOPP. The median age was 28 years with a range of 19 to 47 years; median follow-up was 14 months (range 1 to 90 months). All patients received 4 cycles of eBEACOPP; 11 patients continued their therapy with 4 cycles of sBEACOPP; in 3 patients ABVD was given because of severe toxicity, while in one patient with lung toxicity COPP was the therapy of choice after eBEACOPP. Results: Complete remission and partial remission has been achieved in 10 and 5 patients, respectively. The response to treatment was 100 %. In 5 patients with PR, radiotherapy was given after chemotherapy. After the median of 14 months follow-up the probability of progression-free survival and overall survival is 100 %. The majority of patients experienced serious hematological toxicity and 5 patients (33 %) had to be admitted to hospital because of febrile neutropenia. Discussion and conclusion: This study confirms the efficacy of eBEACOPP protocol, and the results are similar with the reported data. However, the number of patients and relatively short follow-up is the weakness of this study. It has to be stressed out that relapse of Hodgkin lymphoma was not reported. Toxicity is a serious problem, especially hematological toxicity with febrile neutropenia

Ulceracije gingive u bolesnice s akutnom mijeloidnom leukemijom: prikaz slučaja i pregled literature

A 40-year-old female patient was admitted to the Department of Oral Medicine due to oral ulcerations. Oral ulcerations were present on vestibular mucosa above teeth 21, 22, 25 and 26 and were 1 cm in diam-eter, and also around teeth 45 and 46. The patient had prolonged neutropenia due to therapy-related myelodysplastic syndrome that progressed to therapy-related acute myeloid leukemia. Initially, the pa-tient was successfully treated with polychemotherapy for non-Hodgkin lymphoma. Unfortunately, many toxic complications ensued, such as peripheral neuropathy, dilated cardiomyopathy and therapy-related myelodysplastic syndrome/therapy-related acute myeloid leukemia. The onset of therapy-related myelo-dysplastic syndrome was less than six months after initiation of chemotherapy treatment, which was ra-ther early, but cytogenetic changes (monosomy 5 and 7) were consistent with the diagnosis. Upon admis-sion to our Department, microbiological swabs were obtained and were all negative, while x-ray finding showed that ulcerations did not have dental cause. Biopsy was not obtained as the patient had severe neutropenia and thrombocytopenia. While viral and fungal swabs were negative, Stenotrophomonas maltophilia was cultured from the oral cavity. Thus, differential diagnoses are listed in this report. Neutro-penic ulcerations did not heal albeit extensive medicamentous oral and systemic treatments were applied and the patient died.Bolesnica u dobi od 40 godina primljena je na Zavod za oralnu medicinu zbog oralnih ulceracija. Oralne ulceracije promjera 1 cm bile su prisutne na vestibularnoj sluznici iznad zuba 21, 22, 25 i 26, a također i oko zuba 45 i 46. Bolesnica je imala produljenu neutropeniju uslijed mijelodisplastičnog sindroma povezanog s terapijom, koji je pro-gredirao u akutnu mijeloidnu leukemiju povezanu s terapijom. U početku je bolesnica uspješno liječena polikemote-rapijom za non-Hodgkinov limfom. Nažalost, uslijedile su mnoge toksične komplikacije poput periferne neuropatije, proširene kardiomiopatije i mijelodisplastičnog sindroma povezanog s terapijom/akutne mijeloidne leukemije pove-zane s terapijom. Terapijski mijelodisplastični sindrom pojavio se u manje od šest mjeseci nakon započinjanja liječenja kemoterapijom, što je bilo prilično rano, ali su citogenetske promjene (monosomija 5 i 7) bile u skladu s dijagnozom. Nakon dolaska na naš Zavod učinjeni su mikrobiološki brisevi i svi su bili negativni, a rendgenski nalaz je isključio odontogenu etiologiju ulceracija. Biopsija nije učinjena, jer je bolesnica imala tešku neutropeniju i trom-bocitopeniju. Iako su virusni i gljivični brisevi bili negativni, Stenotrophomonas maltophilia izolirana je iz usne šup-ljine. Stoga su u ovom prikazu navedene različite dijagnoze. Unatoč ekstenzivnim oralnim i sistemskim tretmanima neutropenične ulceracije nisu zacijelile, a bolesnica je preminula

FNA Based Diagnosis of Head and Neck Nodal Lymphoma

Fine-needle aspiration (FNA) biopsy has become a well established technique in the diagnosis, staging, and follow-up of patients with head and neck lesions. As in lymphoma diagnostics, FNA serves as a screening method in evaluating potentially affected lymph node for open or core biopsy. According to the World Health Organization classification of lymphoid neoplasms, today it is important to recognize cell morphology and reveal its phenotype, then combine it with different genotypic information and clinical data to provide appropriate therapy. The aim of this study was to assess the efficacy of FNA and immunocytochemistry based lymphoma diagnostic in head and neck region. We conducted a retrospective study during a period of three years where cases with either FNA diagnosis or clinical suspicion of newly recognized or relapsing lymphoma were reviewed. In the study were included patients that were referred to our laboratory from hematology department, in whom head and neck lymphadenopathia was found and lymph node FNA preceded other procedures. Two hundred eighty-five aspirations from 248 patients fulfilled study criteria. Adequate specimens were diagnosed as lymphoma in 100 cases (36%), in 65 male and 35 female patients, 76 in patients with newly discovered disease and 24 in patients with prior lymphoma diagnosis. Overall sensitivity of FNA specimens in the diagnosis of head and neck lymphomas was 90%, specificity 88%, predictive value of a positive result 97%, and predictive value of negative result 61%. Based on our results FNA corroborated with immunophenotyping by immunocytochemistry can be method of choice in primary lymphoma diagnosis as a method complementary to histopathology in lymphoma diagnostics

Simultana pojava oralnog i kožnog anaplastičnog limfoma velikih T stanica

We present case of oral and skin anaplastic T-cell lymphoma in a 68-year-old woman. The patient presented with extensive ulcerations and necrotic tissue on the left mandibular gingiva. Orthopantomogram finding showed extensive necrolytic lesions of the adjacent mandible. Biopsy finding of oral lesions and subsequently of the skin confirmed the diagnosis of anaplastic T-cell lymphoma. The bridge on the teeth 35-37 was taken out. After three cycles of chemotherapy, oral lesions subsided, unlike skin lesions. Dentists should be aware that differential diagnosis when dealing with oral ulcerations might be the result of certain malignant hematologic diseases.U radu se prikazuje slučaj oralnog i kožnog anaplastičnog limfoma velikih T stanica u 68-godišnje osobe. U bolesnice su na prvom pregledu uočene opsežne ulceracije i nekrotično tkivo u području gingive na mandibuli lijeve strane lica. Na ortopantomogramu su se vidjele opsežne nekrolitične lezije na kosti mandibule toga dijela. Patohistološki nalaz sluznice usne šupljine, a poslije i kože potvrdio je dijagnozu anaplastičnog limfoma velikih T stanica. Most na zubima 35-37 je izvađen. Nakon tri ciklusa kemoterapije oralne lezije su se povukle, za razliku od kožnih lezija. Stomatolozi pri diferencijalnoj dijagnostici oralnih ulceracija moraju imati na umu i moguću povezanost tih lezija s malignim hematološkim bolestima

The Effect of Scaling and Root Planing on the Clinical and Microbiological Parameters of Periodontal Diseases

Postojanje parodontnih patogena u subgingivnoj flori parodontitisa rizik je za napredovanje parodontne bolesti. Zato mikrobiološka dijagnostika ima opravdanu indikaciju u otkrivanju patogena, praćenju uspjeha terapije i ishoda bolesti. Svrha ovoga rada bila je prikazati učinak struganja i poliranja korijena (SRP) na kliničke i mikrobiološke čimbenike u 28 pacijenata s kroničnim i agresivnim parodontitisom. Klinička procjena i mikrobiološko testiranje provedeni su prije mehaničke terapije (SRP) i tri mjeseca nakon terapije. Klinički je utvrđeno postojanje ili nepostojanje bakterijskoga plaka i gingivnoga krvarenja, te je određena dubina sondiranja i gubitak pričvrstka prije struganja i poliranja korijena te tri mjeseca nankon toga.Uzorci subgingivnoga plaka uzeti iz parodontnih džepova analizirani su tehnikom lančane reakcije polimeraze (PCR) na nazočnost sedam bakterijskih patogena. Rezultati kliničkih pokazatelja i čestoća bakterijskih vrsta analizirani su prije i poslije terapije Wilcoxson- testom rangova. Srednja vrijednost dubine sondiranja izrazito se je smanjila, od 3,9 na 3 mm. Gubitak pričvrstka smanjio se je umjereno, i to od 4,1 na 3,8 mm. Srednja vrijednost plaka i gingivnoga krvarenja također su smanjeni nakon terapije. Čestoća subgingivnih patogena u ispitanika bila je sljedeća: samo jedna patogena vrsta nađena je u 28,6% ispitanika, dvije vrste u 46,4% i tri u 14,3% ispitanika. Najčešće zastupljeni ispitivani patogeni bili su: Bacteroides forsythus u 85,7%, Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans (A.a.) i Fusobacterium nucleatum u 32,1% ispitanika. Nakon terapije čestoća patogena umjereno se je smanjila. Ukupni broj ispitivanih patogena smanjio se je u 12 ispitanika i taj nalaz bio je statistički znatan (p=0,001). U 16 ispitanika broj patogena ostao je isti, a nije se povećao ni u jednog ispitanika. Nalazi pokazuju da se struganjem i poliranjem korijena u liječenju parodontitisa djelotvorno postiže kliničko i mikrobioloπko poboljšanje smanjenjem čestoće patogena odgovornih za napredovanje bolesti.The occurence of periodontal pathogens in subgingival flora in periodontitis is a risk for periodontal disease progression. Therefore microbiologic diagnostic procedures are justifiably indicated in the detection of pathogens, monitoring of therapy success and outcome of the disease. The aim of this study was to show the effect of scaling and root planing on clinical and microbiological factors in 28 patients with chronic and aggressive periodontitis. Clinical assessment and microbiological testing were performed prior to, and three months after mechanical therapy. The presence or absence of bacterial plaque, gingival bleeding, pocket depth and attachment loss were assessed before and three months after scaling and root planing. Samples of subgingival plaque taken from periodontal pockets, were analysed by polymerase chain reaction technique for the presence of seven bacterial pathogens. Results of clinical parameters and bacterial prevalence were analysed before and after therapy by Wilcoxon Rank test. The mean pocket depth significantly decreased from 3.9 to 3.0 mm. Clinical attachment level decreased moderately from 4.1 to 3.8 mm. Mean plaque and gingival bleeding values also decreased after therapy. The prevalence of subgingival pathogens in relation to subjects was as follows: only one pathogenic species was found in 28.6%, two were found in 46.4% and three in 14.3% of subjects. The most prevalent pathogens were bacteroides forsythus in 85.7%, Porphyromonas gingivalis in 32.1%, Actinobacillus actinomycetemcomitans and Fusobacterium in 32.1% of subjects. After therapy the prevalence of pathogens decreased moderately. The total number of tested pathogens decreased in 12 subjects and this result was statistically significant. (p=0.001). In 16 subjects the number of pathogens was the same, and did not increase in any of the subjects. The results indicate that the effect of scaling and root planing in the treatment of periodontitis was effective in achieving clinical and microbiological improvement by decreasing the prevalence of pathogens responsible for disease progression

Simultana pojava oralnog i kožnog anaplastičnog limfoma velikih T stanica

We present case of oral and skin anaplastic T-cell lymphoma in a 68-year-old woman. The patient presented with extensive ulcerations and necrotic tissue on the left mandibular gingiva. Orthopantomogram finding showed extensive necrolytic lesions of the adjacent mandible. Biopsy finding of oral lesions and subsequently of the skin confirmed the diagnosis of anaplastic T-cell lymphoma. The bridge on the teeth 35-37 was taken out. After three cycles of chemotherapy, oral lesions subsided, unlike skin lesions. Dentists should be aware that differential diagnosis when dealing with oral ulcerations might be the result of certain malignant hematologic diseases.U radu se prikazuje slučaj oralnog i kožnog anaplastičnog limfoma velikih T stanica u 68-godišnje osobe. U bolesnice su na prvom pregledu uočene opsežne ulceracije i nekrotično tkivo u području gingive na mandibuli lijeve strane lica. Na ortopantomogramu su se vidjele opsežne nekrolitične lezije na kosti mandibule toga dijela. Patohistološki nalaz sluznice usne šupljine, a poslije i kože potvrdio je dijagnozu anaplastičnog limfoma velikih T stanica. Most na zubima 35-37 je izvađen. Nakon tri ciklusa kemoterapije oralne lezije su se povukle, za razliku od kožnih lezija. Stomatolozi pri diferencijalnoj dijagnostici oralnih ulceracija moraju imati na umu i moguću povezanost tih lezija s malignim hematološkim bolestima

High-dose ifosfamide and mitoxantrone (HDIM) in patients with relapsed or refractory Hodgkin's lymphoma

Relapsed/refractory Hodgkin's lymphoma (HL) is treated with salvage chemotherapy and autologous stem cell transplantation (ASCT). Optimal chemotherapy is unknown. We retrospectively analyzed outcomes of 58 patients treated with 2 cycles of high-dose ifosfamide and mitoxantrone (HDIM). HDIM consisted of ifosfamide 5 g/m(2)/day and MESNA 5 g/m(2)/day in continuous 24-h infusion (days 1 and 2), MESNA 2.5 g/m(2) over 12 h (day 3), and mitoxantrone 20 mg/m(2) (day 1) administered every 2 weeks. Stem cells were collected after the first cycle. Responding patients proceeded to ASCT. Toxicity was acceptable. Stem cell mobilization was successful in 96 % of patients. Overall response rate was 74 % (89 % in relapsing and 45 % in refractory patients) with 31 % complete remissions. After a median follow-up of 54 months, 5-year event-free survival was 56 % (69 % for relapsing and 35 % for refractory patients), and 5-year overall survival was 67 % (73 % for relapsing and 55 % for refractory patients). Significant adverse prognostic factors were refractoriness to previous therapy and HDIM failure. No differences in outcomes were noted between patients with early and late relapses or between complete and partial responders. HDIM is a well-tolerated and effective regimen for relapsed and refractory HL with excellent stem cell mobilizing properties. Patients failing HDIM may still benefit from other salvage options